Axial-Selective H/D Exchange of Glycine-Derived 1H-Benzo[e][1,4]diazepin-2(3H)-ones: Kinetic and Computational Studies of Enantiomerization

作者：Carlier Paul R^*; Sun Yang Sheng; Hsu Danny C; Chen Qiao Hong

来源：Journal of Organic Chemistry, 2010, 75(19): 6588-6594.

DOI：10.1021/jo1010608

Glycine-derived 1H-benzo[e][1,4]diazepin-2(3H)-ones (BZDs) 5d-g featuring C9- and N1-substitution exhibit enantiomerization barriers too high to be measured by (1)H NMR coalescence experiments. To address this problem, we found that room-temperature H/D exchange of these compounds is remarkably selective, affording only the axial-d(1) isotopomers. (1)H NMR spectroscopy was then employed to measure the rate of conformational inversion of these d(1)-compounds at elevated temperatures. These studies reveal the highest enantiomerization barriers (up to 28 kcal/mol) ever determined for a BZD. Density functional theory calculations match the experimental enantiomerization barriers within 1.2 kcal/mol.

• 出版日期2010-10-1
• 单位美国弗吉尼亚理工大学(Virginia Tech)